DESCRIPTION (provided by investigator): The organization of macromolecular structures is the missing link in our understanding of the properties of proteins and biological function. The need to find the detailed relationship between biological function and macromolecular structure is, thus, undisputed in almost all areas of biology. The introduction of green fluorescent protein (GFP) has made it possible to study structure-function relationships at the cellular level and started a revolution in cell biology. However, only electron microscopy (EM) provides sufficient resolution to study the organization of macromolecular structures, and the lack of a reporter gene for EM has hampered genetic approaches in fine structural research for decades. Recently, we introduced horseradish peroxidase (HRP) cDNA as a genetic marker that can label entire neurons without destroying the fine structure. This marker, together with modern EM approaches (e.g., high resolution electron tomography), has a great potential to advance the field of neuroscience and all areas of cell biology by expanding our knowledge of macromolecular organization.